The First Human Application of an F-18-Labeled Tryptophan Analog for PET Imaging of Cancer

Mol Imaging Biol. 2024 Feb;26(1):29-35. doi: 10.1007/s11307-023-01877-8. Epub 2023 Nov 27.

Abstract

Purpose: Preclinical studies showed the tryptophan analog PET radiotracer 1-(2-18F-fluoroethyl)-L-tryptophan (18F-FETrp) to accumulate in various tumors, including gliomas, and being metabolized via the immunosuppressive kynurenine pathway. In this first-in-human study, we tested the use 18F-FETrp-PET in patients with neuroendocrine and brain tumors.

Procedures: We applied dynamic brain imaging in patients with gliomas (n = 2) and multi-pass 3D whole-body PET scans in patients with neuroendocrine tumors (n =4). Semiquantitative analysis of organ and tumor tracer uptake was performed using standardized uptake values (SUVs). In addition, organ dosimetry was performed based on extracted time-activity curves and the OLINDA software.

Results: Neuroendocrine tumors showed an early peak (10-min post-injection) followed by washout. Both gliomas showed prolonged 18F-FETrp accumulation plateauing around 40 min and showing heterogeneous uptake including non-enhancing tumor regions. Biodistribution showed moderate liver uptake and fast clearance of radioactivity into the urinary bladder; the estimated effective doses were similar to other 18F-labeled radioligands.

Conclusions: The study provides proof-of-principle data for the safety and potential clinical value of 18F-FETrp-PET for molecular imaging of human gliomas.

Keywords: Fluorine-18-labeled tryptophan analog; Glioma; Indoleamine 2,3-dioxygenase; Kynurenine pathway; Molecular imaging; PET; Radiotracer; Tryptophan metabolism.

MeSH terms

  • Glioma*
  • Humans
  • Neuroendocrine Tumors*
  • Positron-Emission Tomography / methods
  • Tissue Distribution
  • Tryptophan / metabolism

Substances

  • Tryptophan